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Published on: January 27, 2018
Temporal dissection of T-bet functions.
Jennifer L Matsuda1, Thaddeus C George, James Hagman
1Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Science Center, 1400 Jackson Street, Denver, CO 80206, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|March 7, 2007
Summary
T-bet transcription factor activity is crucial for immune cell function. Researchers developed a controllable T-bet system to show it directly regulates key immune genes like IFN-gamma, CD122, and CxCR3.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- T-bet is a T-box family transcription factor regulating immune gene expression.
- It directs the Th1 genetic program in CD4(+) lymphocytes.
- T-bet influences NK and NKT cell development and trafficking via CD122 and CxCR3.
Purpose of the Study:
- To define the temporal requirements of T-bet activity.
- To investigate T-bet's role in IFN-gamma production and CD122/CxCR3 regulation.
- To create a system for inducible T-bet control.
Main Methods:
- Generated a fusion protein: T-bet C-terminal domain with mutated human estrogen receptor alpha ligand-binding domain.
- Used 4-hydroxytamoxifen (4-HT) to control T-bet-estrogen receptor alpha expression temporally.
- Analyzed the expression of IFN-gamma, CD122, and CxCR3.
Main Results:
- Demonstrated that IFN-gamma, CD122, and CxCR3 are direct gene targets of T-bet.
- Showed that T-bet activity acutely regulates the expression of these genes.
- Established a method for precise temporal control over T-bet function.
Conclusions:
- T-bet directly controls the expression of IFN-gamma, CD122, and CxCR3.
- The timing of T-bet activity is critical for regulating these immune genes.
- The inducible T-bet system provides a powerful tool for studying immune gene regulation.
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